722. Risk Factors for Infection or Colonization with Ceftolozane/Tazobactam Non-Susceptible Extensively β-Lactam Resistant Pseudomonas aeruginosa

Abstract Background Treatment of infections due to multidrug resistant (MDR) Pseudomonas aeruginosa is complicated by co-resistance amongst traditional anti-pseudomonal β-lactams, as 50% of MDR isolates exhibit extensive β-lactam resistance (EBR, non-susceptible to cefepime, ceftazidime, piperacillin/tazobactam, and meropenem). Ceftolozane/tazobactam (C/T) was developed to combat MDR and EBR P. aeruginosa. Unfortunately, C/T resistance has proliferated. We designed this retrospective case-control study to identify risk factors for C/T non-susceptibility (NS) amongst EBR P. aeruginosa. Methods Between 2015 to 2020, hospitalized adult patients infected or colonized with EBR P. aeruginosa were identified. C/T susceptibility was defined per the 2023 Clinical and Laboratory Standards Institute (CLSI) guidelines (susceptible (S) if minimum inhibitory concentration (MIC) ≤ 4 mg/L, NS if MIC ≥ 8 mg/L). Patients with an EBR P. aeruginosa NS to C/T were classified as cases, whereas those with S isolates were controls. Patients with multiple EBR P. aeruginosa isolates over the study period were only included once. If a patient had a C/T NS isolate, they were classified as cases and the first C/T NS isolate was included as the index culture. If the patient did not have a C/T NS isolate over the study period, they were considered a control and the first C/T S isolate was the index culture. Bivariate and multivariate modeling was performed to identify independent predictors for C/T NS. Results 188 unique patients with C/T susceptibility performed were included in the study; 96 (51%) were C/T NS and 92 (49%) were C/T S. Table 1 shows the bivariate comparisons of key baseline characteristics between groups. Independent predictors of C/T NS are displayed in table 2. Conclusion Independent predictors for C/T NS amongst EBR P. aeruginosa isolates were a history of cancer, cystic fibrosis, and isolation of EBR P. aeruginosa in the past 90 days. While receipt of cefepime or ceftazidime in the past 90 days was associated with C/T NS in bivariate comparisons, the association did not remain in multivariate modeling. C/T exposure was not a statistically significant risk factor, but it was numerically associated with NS and the lack of significance was likely due to the small number of patients (n = 15) who received it. Disclosures Virginia M. Pierce, MD, FIDSA, UpToDate, Inc.: Authorship royalties jason M. Pogue, PharmD, AbbVie: Advisor/Consultant|Entasis: Advisor/Consultant|Ferring: Advisor/Consultant|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Qpex: Advisor/Consultant|Shionogi: Advisor/Consultant


Background. Treatment of infections due to multidrug resistant (MDR)
Pseudomonas aeruginosa is complicated by co-resistance amongst traditional antipseudomonal β-lactams, as 50% of MDR isolates exhibit extensive β-lactam resistance (EBR, non-susceptible to cefepime, ceftazidime, piperacillin/tazobactam, and meropenem).Ceftolozane/tazobactam (C/T) was developed to combat MDR and EBR P. aeruginosa.Unfortunately, C/T resistance has proliferated.We designed this retrospective case-control study to identify risk factors for C/T non-susceptibility (NS) amongst EBR P. aeruginosa.
Methods.Between 2015 to 2020, hospitalized adult patients infected or colonized with EBR P. aeruginosa were identified.C/T susceptibility was defined per the 2023 Clinical and Laboratory Standards Institute (CLSI) guidelines (susceptible (S) if minimum inhibitory concentration (MIC) ≤ 4 mg/L, NS if MIC ≥ 8 mg/L).Patients with an EBR P. aeruginosa NS to C/T were classified as cases, whereas those with S isolates were controls.Patients with multiple EBR P. aeruginosa isolates over the study period were only included once.If a patient had a C/T NS isolate, they were classified as cases and the first C/T NS isolate was included as the index culture.If the patient did not have a C/T NS isolate over the study period, they were considered a control and the first C/T S isolate was the index culture.Bivariate and multivariate modeling was performed to identify independent predictors for C/T NS.
Results.188 unique patients with C/T susceptibility performed were included in the study; 96 (51%) were C/T NS and 92 (49%) were C/T S. Table 1 shows the bivariate comparisons of key baseline characteristics between groups.Independent predictors of C/T NS are displayed in table 2.

Conclusion.
Independent predictors for C/T NS amongst EBR P. aeruginosa isolates were a history of cancer, cystic fibrosis, and isolation of EBR P. aeruginosa in the past 90 days.While receipt of cefepime or ceftazidime in the past 90 days was associated with C/T NS in bivariate comparisons, the association did not remain in multivariate modeling.C/T exposure was not a statistically significant risk factor, but it was numerically associated with NS and the lack of significance was likely due to the small number of patients (n = 15) who received it.
Disclosures.Virginia M. Pierce, MD, FIDSA, UpToDate, Inc.: Authorship royalties jason M. Pogue, PharmD, AbbVie: Advisor/Consultant|Entasis: Advisor/ Consultant|Ferring: Advisor/Consultant|GSK: Advisor/Consultant|Merck: Advisor/ Consultant|Merck: Grant/Research Support|Qpex: Advisor/Consultant|Shionogi: Advisor/Consultant 1 Loma Linda University, Loma Linda, California 2 Andrews Memorial Hospital, Kingston, Kingston, Jamaica 1 Washington University in St. Louis, Lexington, KY 2 Amrita Institute of Medical Sciences and Research Center, kochi, Kerala, India 3 Amrita Institute of Medical Sciences, Kochi, Kerala, India 4 Amrita Institute of Medical Sciences, Kochi, Kochi, Kerala, India 5 Washington University School of Medicine in St. Louis, Saint Louis, Missouri 6 Washington University -School of Medicine, St. Louis, MO 7 University of Maryland School of Medicine, Baltimore, MD TM mSuperCARBA TM ) within 24 hours of collection for CRE isolation.Identification and susceptibility of presumed CRE isolates were confirmed by VITEK2.The modified carbapenem inactivation (mCIM) test and the EDTA carbapenem inactivation method (eCIM) were used to assess carbapenemase production.Information on CRE colonization risk factors (hospitalization and ICU stay in last one year, transfer from outside hospital, long-term hemodialysis) was collected.